miR-140-5p suppresses BMP2-mediated osteogenesis in undifferentiated human mesenchymal stem cells

AbstractHuman mesenchymal stem cells (hMSCs) have self-renewal and differentiation capabilities but the regulatory mechanisms of MSC fate determination remain poorly understood. Here, we aimed to identify microRNAs enriched in hMSCs that modulate differentiation commitments. Microarray analysis revealed that miR-140-5p is commonly enriched in undifferentiated hMSCs from various tissue sources. Moreover, bioinformatic analysis and luciferase reporter assay validated that miR-140-5p directly represses bone morphogenic protein 2 (BMP2). Furthermore, blocking miR-140-5p in hMSCs increased the expression of BMP signaling components and critical regulators of osteogenic differentiation. We propose that miR-140-5p functionally inhibits osteogenic lineage commitment in undifferentiated hMSCs

New drugs in prostate cancer

The standard primary treatment for advanced prostate cancer has been hormonal therapy since the 1940s. However, prostate cancer inevitably progresses to castration-resistant prostate cancer (CRPC) after a median duration of 18 months of androgen deprivation therapy. In patients with CRPC, docetaxel has been regarded as the standard treatment. However, survival advantages of docetaxel over other treatments are slim, and the need for new agents persists. In recent years, novel agents, including abiraterone, enzalutamide, cabazitaxel, radium-223, and sipuleucel-T, have been approved for the treatment of CRPC, and more such agents based on diverse mechanisms are under investigation or evaluation. In this article, the authors reviewed the current literature on recent advances in medical treatment of prostate cancer, especially CRPC. In addition, the authors elaborated on novel drugs for prostate cancer currently undergoing investigation and their mechanisms

Efficacy and safety of degarelix in Korean patients with prostate cancer requiring androgen deprivation therapy: Open-label multicenter phase III study

AbstractPurposeTo assess the noninferiority, efficacy, and safety of degarelix in achieving and maintaining testosterone at castrate levels (≤0.5 ng/mL) in Korean patients (CS42) versus non-Asian patients with prostate cancer (PCa).MethodsA Phase III, open-label, multicenter, single-arm trial was conducted in Korean patients with PCa. Degarelix was administered at a starting dose of 240 mg followed by monthly (28-day intervals) maintenance doses of 80 mg (240/80 mg dose regimen) for 7 months. The results were compared with non-Asian patients receiving degarelix 240/80 mg in the CS21 study.ResultsThe estimated difference in the cumulative probabilities of testosterone ≤0.5 ng/mL from Day 28 to Day 196 between the trials was −2.3% (96.7% in CS42 vs. 99.0% in CS21). The lower limit of the 95% confidence interval was −5.5%, i.e., above the predefined noninferiority limit of −10% and thus noninferiority was established. Decreases in serum testosterone, prostate-specific antigen, and luteinizing hormone over time were similar in CS42 and CS21. There were no clinically significant differences in incidence of treatment-emergent adverse events (72% in CS42 vs. 70% in CS21) and changes in clinical chemistry and hematology parameters between the two trials. The most common adverse event was injection-site reaction.ConclusionsOverall, degarelix was effective and well tolerated in Korean patients. Testosterone suppression was noninferior to that in non-Asian patients and safety findings were as would be expected for elderly men with PCa undergoing androgen deprivation therapy

Prostate-specific antigen response rate of sequential chemotherapy in castration-resistant prostate cancer: the results of real life practice

Prostate-specific antigen (PSA) response rate (>50% PSA decline in pretreatment PSA following chemotherapy) carries a significant survival advantage in castration-resistant prostate cancer (CRPC). We compared PSA response rates in first-, second- and third-line chemotherapy after failure of previous chemotherapy according to chemotherapeutic agents. Methods: We retrospectively evaluated the oncological outcomes and PSA response rates of 384 patients with CRPC, who were treated with chemotherapy and had histologically proven adenocarcinoma of the prostate with failure after androgen ablation therapy between 1991 and 2012, at Asan Medical Center. Results: In 384 eligible patients, the median age was 67.5 years. The median pretreatment PSA and initial Gleason scores at baseline were 92.4 ng/mL (range, 2.0 to 6,370 ng/mL) and 9 (range, 6 to 10), respectively. The time from first diagnosis of prostate cancer to CRPC was 23 months (range, 1 to 164 months). As first-line chemotherapy, 245 patients (63.8%) received estramustine, 91 (23.7%) received docetaxel, and 39 (10.2%) received mitoxantrone. The PSA response rates were 39.6%, 51.6%, and 46.2%, respectively. Of 169 patients with second-line chemotherapy, estramustine was 15 (8.9%), docetaxel was 84 (49.7%), and mitoxantrone was 52 (30.8%). PSA response rates were 57.1%, 52%, and 28.0%, respectively. Of 81 patients with third-line chemotherapy, estramustine was 18 (22.2%), docetaxel was 16 (19.8%), and mitoxantrone was 28 (34.6%). The PSA response rates were 41.2%, 53.8%, and 11.1%, respectively. Declines in serum PSA levels of at least 50% occurred more frequently after treatment with docetaxel than with other chemo-agents regardless of second-and third-line chemotherapy. Even in third-line chemothrapy, docetaxel maintained the PSA response rate, whereas the PSA response rate of other agents, including mitoxantrone, decreased in patients in whom prior therapy failed. Conclusions: Docetacel was the most effective chemotherapeutic agent in second- and third-line trials of chemotherapy in Korean CRPC patients. Although docetaxel is not used as first-line chemotherapy, and new agents are not available for therapy in CRPC patients, we can consider docetaxel a second- or third-line chemotherapy in CRPC

Effect of decreased renal function on poor oncological outcome after radical cystectomy

Purpose: To evaluate the impact of preoperative renal impairment on the oncological outcomes of patients with urothelial carcinoma who underwent radical cystectomy. Materials and Methods: We retrospectively reviewed the medical records of patients with urothelial carcinoma who underwent radical cystectomy from 2004 to 2017. All patients who underwent preoperative 99mTc-diethylenetriaminepentaacetic acid renal scintigraphy (DTPA) were identified. We divided the patients into two groups according to their glomerular filtration rates (GFRs): GFR group 1, GFR≥90 mL/min/1.73 m2; GFR group 2, 60≤GFR<90 mL/min/1.73 m2. We included 89 patients in GFR group 1 and 246 patients in GFR group 2 and compared the clinicopathological characteristics and oncological outcomes between the two groups. Results: The mean time required for recurrence was 125.5±8.0 months in GFR group 1 and 85.7±7.4 months in GFR group 2 (p=0.030). The mean cancer-specific survival was 131.7±7.8 months in GFR group 1 and 95.5±6.9 months in GFR group 2 (p=0.051). The mean overall survival was 123.3±8.1 months in GFR group 1 and 79.5±6.6 months in GFR group 2 (p=0.004). Conclusions: Preoperative GFR values in the range of 60≤GFR<90 mL/min/1.73 m2 are independent prognostic factors for poor recurrence-free survival, cancer-specific survival, and overall survival in patients after radical cystectomy compared with GFR values of ≥90 mL/min/1.73 m2

Hybrid ileal pouch with concomitant anti-refluxing and refluxing ureteroileal anastomosis

Abstract Purpose We report our preliminary experience of using a hybrid ileal pouch, assessing oncologic outcomes, complications, voiding, and renal function. Methods The study included 25 patients with bladder cancer treated with radical cystectomy with a hybrid ileal pouch with concomitant anti-refluxing and refluxing anastomosis, performed by a single surgeon. The patients were divided into two groups (first and last cases) according to the surgery date. Postoperative complications, separate renal function by renal scan, voiding function by uroflowmetry with residual urine, and oncologic outcomes were assessed. Results The surgery duration was shorter in the last cases than the first cases. The voiding volume increased with time. There were 23 cases of grade 3 complication in 12 patients and one case of grade 4 complication (sepsis). In the first cases, ureterovesical stenosis occurred in five cases, whereas in the last cases, there were no cases of stenosis. In separate renal function, there was no difference between the left and right side or between the first and last cases. Conclusions The hybrid ileal pouch showed acceptable oncologic and functional outcomes and complications; therefore, it can be used according to the appropriate surgical situation with a relatively short bowel segment during neobladder construction

Therapeutic effect of human mesenchymal stem cell-conditioned medium on erectile dysfunction

Purpose: Owing to the safety and cost effectiveness of conditioned medium (CM), its therapeutic effects have attracted signifi-cant attention from many researchers. To date, numerous studies have been conducted on CM; however, little has been done with regard to erectile dysfunction (ED). In this research, the potential of human mesenchymal stem cell-derived CM (MSC-CM) for the treatment of ED was investigated. Materials and Methods: A high concentration of MSC-CM was prepared through 3D spheroid culturing with bone marrow-derived MSCs and cut-off filtering. The composition of CM was analyzed using biochemical assays, and the effect of the preparation process on the quality of CM was investigated. The therapeutic effects of MSC-CM were evaluated through ani-mal studies using a cavernous nerve (CN) injury rat model. Results: 3D spheroid culturing afforded a 278-fold increase in the total protein content of CM, as compared to that from 2D cultures; the protein concentration increased by 19 times on increasing the centrifugation time for cut-off filtering. Biochemi-cal assays indicated that the CM contains various types of angiogenic, neurotrophic, and anti-inflammatory factors. Histologi -cal assay results showed that MSC-CM has angio-and neuro-trophic effect in a CN injury rat model in vivo, and these thera-peutic effects appear in a dose-dependent manner. Conclusions: The experimental results confirmed the therapeutic effect of MSC-CM in healing damaged cavernosal tissue and restoring erectile function. These results successfully demonstrated that MSC-CM has significant potential for the treatment of ED